Formulations such as cleansing formulations (e.g. shampoos, facial soaps, etc.) generally cause irritation to the ocular membrane when coming in contact with the eyes. This imposes an unpleasant feeling to the user, which results in stinging or tearing, and in certain cases may even be harmful. This problem is of particular importance in shampoos designated for use by infants and children.
Cleansing formulations are irritating mainly because they comprise surfactants, especially ionic surfactants, which interact with the mucous membrane, and because the pH of such formulation differs from the normal pH of the eye being 7.0 to 7.3.
Recent studies conducted by the U.S. environmental protection agency (EPA) revealed that human blood and lipid tissues contain up to 400 hazardous chemicals originating from cosmetics and food products. Those chemicals may cause various side effects, such as headaches, eye irritation, skin irritation, and long term effects such as the development of various cancer diseases.
Such studies have encouraged the development of “natural” cosmetic compositions; however, to date, none of the available compositions are 100% natural body soaps/shampoos. Several of the products known today contain mainly synthetic ingredients, with the addition of a very small amount of natural ingredients. Other known products contain a higher percentage of natural ingredients; however, they are mainly composed of synthetic materials. The most natural known products today contain chemically modified natural ingredients.
Products composed of natural ingredients may also contain irritating substances that cause tear, itching and redness in the eye when coming in contact with the ocular membrane. Thus, problems associated with the development of a product that is wholly natural become vastly more complex where the product must also demonstrate no irritancy to the user's eyes. This development is particularly important in products intended for use in babies and young children.
WO2012/077120 discloses natural formulations for skin or hair for providing cleansing, moisturizing, minimizing skin imperfections, reducing skin oiliness, providing fragrance to the hair or skin and reliving skin dryness and signs of aging.
FR2810550 discloses solutions for use in medicine containing homogeneous extracts of the white and yolk of quail eggs for the treatment of allergies such as eye irritation.
ES2333574 discloses natural compositions for treating skin irritation containing chicken egg yolk.
General Description
The inventors of the present invention have developed a class of products comprising a combination or a mixture of naturally occurring ingredients which has a suppressing or attenuating effect on the ocular irritancy of formulations which come into contact with ocular membranes; such formulations were found to be useful on cosmetic formulations as well as on therapeutic formulations such as, for example, shampoos, conditioners, soaps, make-up removers, eye-drops, and others.
The preparations of the invention have been found to be efficient in suppressing or attenuating ocular or skin irritancy, per se, and also endow other formulations which are known or expected to have a degree of irritancy with reduced or diminished irritating effects.
Thus, in accordance with a first aspect of the invention, there is provided a formulation comprising a combination of lecithin and egg yolk, at least one natural oil, and optionally hyaluronic acid and/or hyaluronate, said formulation being capable of reducing, diminishing or ameliorating irritation to an eye region or to a skin region surrounding the eye.
In another aspect, the invention provides a formulation comprising a combination of lecithin and egg yolk, at least one natural oil, and optionally hyaluronic acid and/or hyaluronate, said formulation being capable of reducing, diminishing or ameliorating irritation to an eye.
In a further aspect, the invention provides a formulation comprising
1—at least one of lecithin and egg yolk,
2—at least one natural oil, and
3—optionally hyaluronic acid and/or hyaluronate,
said formulation being adapted for adding to a skin care formulation or hair care formulation exhibiting irritation to an eye region or to a skin region surrounding the eye, the formulation capable of reducing, diminishing or ameliorating irritation caused by the skin care formulation coming in contact with the eye region or the skin region surrounding the eye.
The low irritancy formulation is thus herein classified as a minimally or non-irritating formulation. As known in the field of the invention, such formulations are typically known as “tear-free” formulations.
The low irritancy formulation may thus be used as a baby shampoo, baby bath, mild skin cleanser, facial skin cleanser, sensitive skin cleanser and other cleansing formulations suitable for use on infant skin.
The formulations of the invention may similarly be utilized on human infant and adult skin regions, eyes, or skin regions surrounding the eyes.
In another aspect, the formulation comprising at least one of lecithin and egg yolk, at least one natural oil, and optionally hyaluronic acid and/or hyaluronate may be used for any purpose in which low irritancy to the skin and/or eyes is desirable. The formulation may for example be utilized as an additive (add on) to formulations which are irritating to the (human or non-human) eyes or skin; thereby rendering such irritating formulations with a reduced or diminished irritancy.
In some embodiments, the formulation is selected from a baby shampoo, baby bath, mild skin cleanser, facial skin cleanser, sensitive skin cleanser and cleansing formulations suitable for use on human infant skin; or adult shampoo, adult bath, mild skin cleanser, facial skin cleanser, sensitive skin cleanser and cleansing formulations suitable for use on human adult skin.
In a further aspect, the invention pertains to the use of any one of the above minimally or non-irritating formulations for the preparation of an additive to an existing formulation, for reducing, diminishing or ameliorating irritation to an eye or a skin region surrounding the eye.
According to the invention, the formulation comprising the naturally occurring ingredients recited hereinabove or below, is adapted to produce the herein referred to non-irritating additive or additive. According to some embodiments, the additive may be stored before it is added to an eye-irritating formulation.
As may be clear to the skilled in the art, the additive of the invention does not substantially alter any one existing characteristics of an irritating formulation, apart from rendering it less irritating or not irritating at all. In other words, properties such as cleaning properties, foaming e.g., of a shampoo formulation, ease of removal by washing, feeling and after-feeling effects are not significantly reduced or attenuated by the addition of a formulation of the invention.
The invention also pertains to a method for suppressing or reducing ocular irritancy of a cosmetic or therapeutic formulation suitable for application to an eye of a subject or to a skin region surrounding an eye of a subject, the formulation being capable of causing irritation to an ocular membrane, the method comprising: mixing prior to application of said formulation to the eye or a skin region surrounding said eye an effective amount of an additive, as defined herein.
The formulations and additives of the invention are capable of suppressing, reducing, delaying, or diminishing any one or more irritating feeling in the eyes of a subject; said irritating feeling being associated with one or more component or ingredient present in a cosmetic or therapeutic formulation to be applied to the eye or a skin region surrounding the eye.
The additive may be applied to the eye prior to, concomitant with or after a cosmetic or therapeutic formulation has been applied to the eye or a skin region surrounding the eye. The additive is typically applied to the cornea of the eye. In some embodiments, the additive is added and mixed into the cosmetic or therapeutic formulation during the manufacture process of said cosmetic or therapeutic formulation; thus rendering said cosmetic or therapeutic formulation tear-free.
Thus, the additive may be in the form of an add-on formulation which may be added to a ready-made cosmetic or therapeutic formulation or may be the cosmetic or therapeutic formulation itself.
It is thus a further object of the invention to provide a non-skin-irritating or non-eye-irritating formulation, either formulation being selected from a cosmetic formulation for application onto a skin region of a subject, a cleansing formulation, a therapeutic topical formulation, an ophthalmic formulation, a solid form formulation or a liquid form formulation, and a cleansing, or therapeutic formulations suitable for infants and children.
As stated above, the formulations of the invention are all natural formulations, namely comprising components and ingredients originating or extracted or obtained or derived from nature. No synthetic ingredients are included in formulations of the invention.
The “lecithin” comprised in formulations of the invention is typically derived from animal or plant sources such as soy beans, eggs, milk, marine sources, rapeseed, cottonseed, and sunflower. In some embodiments, the lecithin is derivable from soy beans and/or egg yolk.
The “natural oils” are typically selected from almond oil, aragan oil, avocado oil, calendula oil, castor oil, coconut oil, grape seed oil, jojoba oil, linseed oil, macadamia oil, meadowfoam oil, olive oil, palm oil, sesame seed oil, sun flower oil, vegetable squalane and squalane, oil from eggs or yolk, jojoba wax and lanolin.
In some embodiments, the natural oils are selected from castor oil, jojoba oil, jojoba wax, meadowfoam oil, vegetable squalane and squalane, oil from eggs or yolk, lanolin, bees wax, carnauba wax, candelilla wax, cocoa and animals wax/butter.
In some embodiments, the formulations according to the invention comprise at least one additional additive selected amongst phospholipids (lecithins), polysaccharides, polyols, saponins, salicilates, preservatives, perfumes, natural coloring agents, emollients, non-aqueous or aqueous solvents or mixtures, and other active or non-active components.
In some embodiments, a formulation according to the invention comprises one or more phospholipids and/or one or more polysaccharide.
In some embodiments, the formulation further comprises at least one emollient and/or at least one polyol. The polyol is selected from mannitol, glycerol, zemea, trehalose, fructose, mannose, sucrose, glucose, dextrose, trehalose, mannitol, lactose, rhamnose, sorbitol, honey extracts, glycol, diols and polyols such as vegetable glycerin, 1,2-butanediol, propylene glycol, ethanol. Other polyols included are betaine, natural urea, lactic acid and other alpha hydroxy acids.
In some embodiments, the polyol is selected from mannitol, glycerol, zemea and trehalose.
In some embodiments, the phospholipid is soy bean lecithin.
In some embodiments, the polysaccharide is selected, in a non-limiting fashion, from xanthan, Tragacanth gum, Carrageenan gum, Alginates, Konjac gum Agar-Agar, gum Arabic, Guar gum, Starch, Gellan gum, Pectin, Cellulose, Welan and Dituan gum, Locust bean gum, Dammar gum, Kauri gum, Spruce gum, Fenugreek gum and gum anima, sclerotium gum and poly glutamic acid.
In some embodiments, the polysaccharide is selected from sodium hyaluronate, xanthan gum, Carrageenan, Konjac gum, Tragacanth gum, Alginates, Guar gum, Locust bean gum, sclerotium gum, and poly glutamic acid
In some embodiments, the emollient is a natural oil selected from jojoba oil and squalene oil.
In some embodiments, the formulation comprises at least one phospholipid, at least one polysaccharide and at least one emollient.
In some embodiments, the formulation according to the invention is the formulation shown in Table 1:
TABLE 1A formulation according to the inventionIngredientChemical FamilySoy-beanPhospholipidsLecithinJojoba oilEmollientSqualene oilEmollientEgg YolkPhospholipids + cholesterol +EmollientSodiumPolysaccharidesHyaluronate
In some embodiments, the sodium hyaluronate may be replaced or combined with at least one other polysaccharide, as exemplified in Table 2.
TABLE 2A formulation according to the inventionIngredientChemical FamilySoy-bean LecithinPhospholipidsJojoba oilEmollientSqualene oilEmollientEgg YolkPhospholipids + cholesterol +EmollientSodiumPolysaccharidesHyaluronateand/orXanthan gumand/orCarrageenan
In some embodiments, the formulation may comprise one or more polyol. In some embodiments, the formulation comprises at least one phospholipid, at least one polysaccharide, at least one polyol and optionally at least one emollient.
In some embodiments, the formulation may comprise at least one preservative.
In other embodiments, the formulation may comprise at least one saponin. In such embodiments, the formulation may comprise at least one phospholipid, at least one polysaccharide, at least one saponin and optionally at least one emollient and/or at least one polyol.
Exemplary formulations are depicted in Table 3 and Table 4.
TABLE 3A formulation according to the inventionIngredientChemical FamilySoy-beanPhospholipidsLecithinJojoba oilEmollientSqualene oilEmollientEgg YolkPhospholipids + cholesterol +EmollientMannitol and/orPoly-olGlycerol and/orZemea and/orTrehalose
TABLE 4A formulation according to the inventionIngredientChemical FamilySoy-bean LecithinPhospholipidsJojoba oilEmollientSqualene oilEmollientEgg YolkPhospholipids + cholesterol +EmollientSodiumPolysaccharidesHyaluronate and/orXanthan gumand/or CarrageenanMannitol and/orPoly-olGlycerol and/orZemea and/orTrehalose
In some embodiments, each of the formulations of the invention, e.g., those depicted in Tables 1-4 comprises at least one saponin.
As used herein, the at least one “saponin” is at least one naturally obtained saponin compound or saponin material, as known in the art. When isolated from a natural source, the at least one saponin may be used in its substantially pure form (namely at least 85%, 87%, 92%, 95%, or 98% purity), or may be used as a saponin-containing extract isolated by a method known in the art or by a method of the invention, as disclosed herein.
In some embodiments, the saponin material is a purified compound of the saponin family.
In other embodiments, the saponin material is a saponin-containing extract. In accordance with the present invention, the saponin-containing extract (herein referred to for the purpose of brevity as “saponin extract”) contains at least between 0.2% and 95 wt % saponins, out of the total weight of the dry content of the extract. In some embodiments, the extract used in accordance with the present invention comprises between 0.2% and 99 wt % saponins out of the total weight of the dry content of the extract.
In some embodiments, the extract used in accordance with the present invention comprises between 10% and 80 wt % saponins out of the total weight of the dry content of the extract. In other embodiments, the extract used in accordance with the present invention comprises between 10% and 60 wt % saponins out of the total weight of the dry content of the extract. In further embodiments, the extract used in accordance with the present invention comprises between 10% and 50 wt % saponins out of the total weight of the dry content of the extract. In additional embodiments, the extract used in accordance with the present invention comprises between 10% and 40 wt % saponins out of the total weight of the dry content of the extract. In still additional embodiments, the extract used in accordance with the present invention comprises between 10% and 30 wt % saponins out of the total weight of the dry content of the extract.
In some embodiments, the extract used in accordance with the present invention comprises between 10% and 20 wt % saponins out of the total weight of the dry content of the extract.
In some embodiments, the extract used in accordance with the present invention comprises between 0.2% and 10 wt % saponins out of the total weight of the dry content of the extract.
The saponin-containing extract may be obtained from any natural source known to comprise saponins. Such natural source may be a plant source, some of which are detailed infra, and also from non-plant sources such as animal sources and marine organisms, such as starfish and sea cucumbers. In some embodiments of the invention, the saponins are extracted from a plant source, naturally grown or genetically modified to have high saponin content.
In some embodiments of the invention, the saponin material is obtained by extraction from a plant source by employing water, alcohol or a water/alcohol solution. In some embodiments, the alcohol is ethanol or methanol.
In some embodiments, the extraction is achieved by employing a water/alcohol solution. In some embodiments, the water/alcohol solution has a water:alcohol ratio of between 80:20 to 20:80. In further embodiments, the water/alcohol solution has a water:alcohol ratio of between 60:40 to 40:60. In further embodiments, the water/alcohol solution has a water:alcohol ratio of between 70:30 to 30:70. In further embodiments, the water/alcohol solution is 80:20 water/alcohol, 60:40 water/alcohol, 50:50 water/alcohol, 40:60 water/alcohol ratio, 20:80 water/alcohol, 70:30 water/ethanol or 30:70 water ethanol.
The extraction time may vary without limitation from 2 to 8 hours, at or above room temperature (20° C.-30° C.), e.g., above 30° C., 40° C., 50° C. or 60° C. In some embodiments, the extraction is carried out at a temperature between 30° C. and 70° C.
In some embodiments, the saponin material is obtained from a plant source. The plant source may be selected from shikakai, soy beans, beans, peas (Pisum sativum), lucerne, tea, spinach, sugar beet, quinoa, liquorice, sunflower, horse chestnut, ginseng, oats, capsicum peppers, aubergine, tomato seed, alliums, asparagus, yam, fenugreek, yucca and ginseng, lucerne, mung beans, Bupleurum falcatum, Camellia oleifera, Camellia sinensis Desmodium adscendens, Gypsophila, Panax quinqufolius, Panax japonicas, Quillaja saponaria, Sapindus delavayi, Sapindus mukorossi, Sapindus marginatus, Sapindus saponaria, Sapindus trifoliatus, Saponaria officinalis, Styrax japonica, and Yucca schidigera or any mixture thereof. Any part of the plant may be used for extracting the saponin material, including leaves, stems, roots, bulbs, blossom and fruit (including the skin, flesh and seed of the fruit).
In some embodiments, the saponin material is an extract of Camellia oleifera, Saponaria officinalis, or Sapindus mukorossi or a mixture thereof.
In other embodiments, the saponin material is an extract of Camellia oleifera, or Sapindus mukorossi or a mixture thereof.
In other embodiments, the saponin material is an extract of Sapindus mukorossi. 
The saponin material obtained from a plant source, e.g., Camellia oleifera, and/or Sapindus mukorossi, may be extracted by treating the plant source in a water/alcohol solution under conditions permitting extraction of the saponin material into the solution. The so-extracted saponin containing material may optionally thereafter be purified by any means known in the art, including: filtration, centrifugation, re-crystallization, distillation, adsorption, chromatographic methods, fractionation, etc.
In some embodiments, the plant source is first dried and ground before being treated in the water/alcohol solution.
In some embodiments, the saponin material is extracted from a plant source following a method comprising:                1. Treating the plant source in a 40:60 to 60:40 water:alcohol solution for a period of time and under conditions permitting extraction of the saponin material from said plant source into said solution, as defined hereinabove;        2. optionally, drying said saponin-containing solution to obtain a saponin-containing solid material; and        3. optionally, purifying said saponin-containing solid material.        
In some embodiments, the water:alcohol solution employed is about 50:50.
In some embodiments, the plant source is one or both of Camellia oleifera and Sapindus mukorossi. In some embodiments, the plant source is Sapindus mukorossi and the saponin material is extracted from the nut shell. In other embodiments, the plant source is Camellia oleifera and in some embodiments the saponin material is extracted from the defatted seed meal of Camellia oleifera. 
In some embodiments, the formulation of the invention is a cosmetic formulation comprising an additive according to the invention.
In other embodiments, the formulation of the invention is a therapeutic formulation comprising an additive according to the invention.
In some embodiments, the additive is selected from the formulations listed in Table 1, Table 2, Table 3 or Table 4 above.
In some embodiments, and for the purpose of demonstrating a cosmetic formulation according to the invention, in Table 5, a shampoo formulation is provided:
TABLE 5A shampoo formulation according to the invention.IngredientChemical FamilySapindus MukorossiSaponinsextract and/orCamellia oleiferaextract and/orQuillaja extractAspen bark (PopulusSalicaceaetremuloides) extractSoy-bean LecithinPhospholipidsJojoba oil and/orEmollientSqualene oilEgg YolkPhospholipids + cholesterol +EmollientSodium HyaluronatePoly saccharidesand/or Xanthan gumand/or CarrageenanMannitol and/orPoly-olTrehalose and/orZemea and/orGlycerol
In some embodiments, an exemplary shampoo of the invention is provided in Table 6:
TABLE 6A shampoo formulation according to the inventionConc. RangeIngredientChemical Familywt %Sapindus MukorossiSaponins0.5-6  extractCamellia oleiferaSaponins0-6extractQuillaja extractSaponins0-6Aspen barkSalicaceae0.1-0.8(Populustremuloides) extractSoy-bean LecithinPhospholipids0.1-5  Jojoba oilEmollient0.2-4  Squalene oilEmollient0.2-4  Egg YolkPhospholipids + cholesterol +0.2-5  EmollientSodium HyaluronatePoly saccharides  0-0.8Xanthan gumPoly saccharides  0-2.5CarrageenanPoly saccharides  0-2.5MannitolPoly-ol  0-2.5GlycerolPoly-ol 0-15ZemeaPoly-ol 0-15optionalTrehalosePoly-ol  0-2.5optionalPerfume  0-1.5
A shampoo formulation of Table 6 is hereinbelow referred to as Shampoo no. 1 (see experimental details below).
In some embodiments, the formulations of the invention comprise a selection of natural ingredients selected from at least one saponin material; at least one phospholipid; at least one emollient; at least one poly saccharide; and at least one alcohol or polyol. Depending on the nature of the formulation, it may further comprise at least one therapeutic agent; at least one coloring agent; at least one solvent, excipient or diluents.
The formulation may be in the form of a solid or liquid ready for use formulation.
Any additive formulation according to the invention may be used as a formulation for reducing irritation of a ready-made formulation for application onto a skin or membrane tissue region of a subject. Thus, the formulations of the invention are also applicable to reduce or diminish irritations of a skin region by a formulation suitable for application on such a region. The formulations of the invention are not solely applicable for reduction of irritation in the eye.